1,5-D-anhydrofructose (hereinafter may be abbreviated as “1,5-AF”) can be produced by using α-1,4-glucan lyase which is an enzyme contained in a certain kind of ascomycete or red alga and using starch or decomposed starch as a substrate. 1,5-D-anhydrofructose has an interesting, peculiar structure, dehydrated form of glucose. It has already been reported that 1,5-AF has antioxidative activity (refer to JP-A 9-505988 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”)) and antimicrobial activity (refer to JP-A 2001-89377). Further, it has been reported in recent studies that 1,5-AF also has an antihyperglycemic effect (refer to JP-A 2003-519660). It has been receiving attention as novel sugar having bioactivity.
Meanwhile, it has been reported that ascopyrone can be prepared from an enzyme reaction of 1,5-D-anhydrofructose (refer to WO03/38084, WO03/38085and WO03/38107). It has been known that ascopyrone is biosynthesized by a certain kind of ascomycete (refer to M. A. Baute., phytochemistry, 33, (1991) 41-45). It has been reported that ascopyrone can also be prepared by causing a fungi extract of Pezizales orders such as Picaria leiocarpa and Anthracobia melaloma and Tuberales orders such as Tuber melanosporum to act on 1,5-D-anhydrofructose.
Ascopyrone P
(2-hydroxymethyl-5-hydroxy-2,3-dihydro-4H-pyran-4-one) was prepared by a group of U.S. scientists in 1978 and 1981 by thermally decomposing amylopectin, amylose and cellulose for the purpose of using ascopyrone P as a staring material for organic synthesis (refer to Shafizadeh, F., et al., Carbohydr. Res., 67, (1978) 433to 447and Stevenson, F., et al., Carbohydr. Res., 90, (1981) 319 to 325).
It has been reported that as in the case of 1,5-D-anhydrofructose, ascopyrone P (hereinafter may be abbreviated as “APP”) also has antioxidative activity and antimicrobial activity (refer to WO02/26060, WO02/26061 and WO00/56838).
Most of antitumor medicines used in clinics at present have a pro-oxidant effect according to their chemical nature and have a high possibility of causing a side effect such as hepatopathy, nephropathy, bone marrow suppression or pneumonopathy. In contrast, 1,5-D-anhydrofructose and ascopyrone have antioxidative activity and also inhibit activation of inflammatory cells. It is assumed that they thereby attenuate such inflammatory tissue damage as seen in antitumor medicines such as bleomycin and cisplatin. Accordingly, by use of the antitumor medicine of the present invention in combination with other antitumor medicines, not only enhancement of antitumor effect but also application to a chemotherapy aid which alleviates side effects can be expected.